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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Molecular Cancer 1/2017

The depletion of PinX1 involved in the tumorigenesis of non-small cell lung cancer promotes cell proliferation via p15/cyclin D1 pathway

Zeitschrift:
Molecular Cancer > Ausgabe 1/2017
Autoren:
Xiao-Peng Tian, Xiao-Han Jin, Mei Li, Wei-Juan Huang, Dan Xie, Jia-Xing Zhang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12943-017-0637-4) contains supplementary material, which is available to authorized users.

Abstract

Background

The telomerase/telomere interacting protein PinX1 has been suggested as a tumor suppressor. However, the clinical and biological significance of PinX1 in human non-small cell lung cancer (NSCLC) is unclear.

Methods

PinX1 gene/expression pattern and its association with NSCLC patient survival were analyzed in cBioportal Web resource and two cohorts of NSCLC samples. A series of in vivo and in vitro assays were performed to elucidate the function of PinX1 on NSCLC cells proliferation and underlying mechanisms.

Results

More frequency of gene PinX1 homozygous deletion and heterozygote deficiency was first retrieved from cBioportal Web resource. Low expression of PinX1 correlated with smoking condition, histological type, T stage, N stage, M stage and TNM stage, and was an independent predictor for overall survival in a learning cohort (n = 93) and a validation cohort (n = 51) of NSCLC patients. Furthermore, knockdown of PinX1 dramatically accelerated NSCLC cell proliferation and G1/S transition, whereas ectopic overexpression of PinX1 substantially inhibited cell viability and cell cycle transition in vitro and in vivo. p15/cyclin D1 pathway and BMP5 might contribute to PinX1-associated cell proliferation and cell cycle transition.

Conclusion

The cost-effective expression of PinX1 could constitute a novel molecular predictor/marker for NSCLC management.
Zusatzmaterial
Additional file 1: Supplementary materials and methods. (DOCX 15 kb)
12943_2017_637_MOESM1_ESM.docx
Additional file 2: Table S1. Area under the receiver-operator curve of PinX1 for each pathological feature in both NSCLC cohorts (DOCX 13 kb)
12943_2017_637_MOESM2_ESM.docx
Additional file 3: Figure S1. Receiver-operator curves (ROC) were used to determine the cut-off score for positive expression of PinX1 protein in both cohorts. The sensitivity and specificity for each outcome were plotted: (A). Gender in learning cohort, (B) M stage in learning cohort, (C) Gender in validation cohort, (D) M stage in validation cohort, (E) T stage in validation cohort, (F) N stage in validation cohort, (G) WHO grade in validation cohort, (H) TNM stage in validation cohort. (TIF 531 kb)
12943_2017_637_MOESM3_ESM.tif
Additional file 4: Figure S2. MTT assay was performed to measure viability of BEAS-2B cells expressing different levels of PinX1. The survival capacity of cells was substantially enhanced in PinX1-silenced BEAS-2B cells (Normal lung epithelial cells). Transfected with PinX1 in BEAS-2B cells displayed a substantial drop in cell viability compared with that of control cells. Each bar represents the mean ± SD of three independent experiments. *, compared to control group (P<0.05). (TIF 226 kb)
12943_2017_637_MOESM4_ESM.tif
Literatur
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